Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021831 (enteropathy)
 4,403 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Examination of the small intestine of pigs with proliferative haemorrhagic enteropathy showed changes consistent with defects in vascular permeability. Early in the disease there were many eosinophils and distension of lacteals and intercellular spaces with proteinaceous material. Later the predominant features were red blood cells and exudate in tissue spaces. This was most severe and extensive at the tips of villi which were covered by a cast of cells and fibrinous exudate. Adenomatous intestinal mucosal cells contained organisms that were free within the apical cytoplasm and were morphologically identical with those seen in the related disease, porcine intestinal adenomatosis. Also these bacteria were seen free in the subepithelial mucosal area, in blood vessels and within membrane-bound vesicles in phagocytic cells in the mucosa and its blood vessels. Mast cells were prominent in some areas as were thrombosed vessels.
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PMID:Pathology of proliferative haemorrhagic enteropathy in pigs. 31 20

A 38-year-old Russian woman (KZ) has been identified as the fourth proposita with the Inab blood group phenotype. Like the first two propositi, she has a chronic intestinal disorder and, as shown for the third proposita, her Inab phenotype is demonstrably inherited. KZ's serum contained anti-IFC, which reacted with a red blood cell (RBC) membrane component with an Mr of 70,000, which is decay accelerating factor (DAF). Her RBCs lacked all Cromer-related blood group antigens and DAF. Her RBCs were no more susceptible than normal control RBCs to lysis in acid lysis or in rabbit or human antibody-initiated complement lysis tests. Northern blots of total RNA isolated from KZ's Epstein-Barr virus-transformed lymphoblasts showed a marked reduction of DAF mRNA when compared with normal. Polymerase chain reaction (PCR) amplification of cDNA confirmed this reduced level of DAF mRNA. Sequencing of the PCR product showed a 44-nucleotide deletion in the mRNA close to the short consensus repeats IIIa/IIIb intron/exon boundary. This deletion results in a change in the reading frame that places a termination codon six amino acids after the deletion. The putative translation product would lack a glycosyl phosphatidyl-inositol linkage site and, therefore, would not be membrane-bound in the RBC.
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PMID:Biochemical studies on red blood cells from a patient with the Inab phenotype (decay-accelerating factor deficiency). 172 Jul 2

Gnotobiotic pigs and conventional hamsters were given suspensions of intestinal mucosa from a pig with proliferative hemorrhagic enteropathy and killed 10 or 21 days later. Affected animals had evidence of marked proliferation of immature enterocytes in the intestinal crypts. Numerous Campylobacter-like organisms were in the cytoplasm of enterocytes, and in some instances, bacteria were closely associated with enterocytes. Some intracellular bacteria lying below the microvillous border were within membrane-bound structures. Immunofluorescence and electron immunogold staining with specific antibodies indicated that these organisms were antigenically different from curved bacteria in the crypt lumen of early lesions. This study indicates that the life cycle of the intracellular organisms may involve entry into crypt enterocytes from the intestinal lumen with subsequent intracellular multiplication.
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PMID:Early lesions of proliferative enteritis in pigs and hamsters. 266 13

Separate suspensions of two strains of ileal symbiont (IS) intracellularis, an obligate intracellular bacterium and the causative agent of porcine proliferative enteropathy, were added to 40 or 80 per cent confluent monolayers of established cultures of rat (IEC-18) or pig enterocytes (IPEC-J2). Peak numbers of intracellular organisms were detected within the enterocytes six days later, but no cytopathic effects were evident. After an initial close association with the cell membrane of the enterocytes, single bacteria were internalised after three hours within membranes-bound vacuoles. The formation of an electron-dense projection between cell membranes and external bacteria was only evident if the bacterial suspensions were centrifuged on to the monolayers. The release of internalised bacteria into the cytoplasm, with the breakdown and loss of membrane-bound vacuoles, was also evident three hours after infection. Internalised bacteria were associated with, but not observed within, coated membrane pits. Mitochondria were closely associated with internalised vacuoles and with released bacteria. Two to six days after infection, multiplication of the bacteria free in the cytoplasm was frequently observed. In infected cells six days after the inoculation of monolayers, groups of bacteria were found within large, balloon-like, cytoplasmic protrusions, and the subsequent release of bacteria from the monolayer provided a means of bacterial exit from the cells. Many events in the in vitro culture model closely resembled events observed at the cellular level in animals infected with IS intracellularis and the model provides a useful basis for investigating the pathogenetic mechanisms of this bacterium.
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PMID:Entry of the bacterium ileal symbiont intracellularis into cultured enterocytes and its subsequent release. 858 2

Carbohydrates are hydrolyzed in the intestinal lumen by specific enzymes to monosaccharides before transport across the brush border membrane of epithelial cells into the cell interior. The enzymes implicated in the digestion of carbohydrates in the intestinal lumen are membrane-bound glycoproteins that are expressed at the apical domain of the enterocytes. Absent or reduced activity of one of these enzymes is the cause of disaccharide intolerance and malabsorption, the symptoms of which are abdominal pain, cramps or distention, flatulence, nausea and osmotic diarrhea. Lactose intolerance is the most common intestinal disorder that is associated with an absence or drastically reduced levels of an intestinal enzyme, in this case lactase-phlorizin hydrolase (LPH). The pattern of reduction of activity has been termed late onset of lactase deficiency or adult type hypolactasia. It was thought that the regulation of LPH was post-translational and was associated with altered structural features of the enzyme. Recent studies, however, suggest that the major mechanism of regulation of LPH is transcriptional. Other forms of lactose intolerance include the rare congenital lactase deficiency and secondary forms, such as those caused by mucosal injury, due to infectious gastroenteritis, celiac disease, parasitic infection, drug-induced enteritis and Crohn's disease. This review will shed light on important strucural and biosynthetic aspects of LPH, the role played by particular regions of the LPH protein in its transport, polarized sorting, and function, as well as on the gene expession and regulation of the activity of the enzyme.
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PMID:Molecular and cellular aspects and regulation of intestinal lactase-phlorizin hydrolase. 1133 11

The kinetics of antibody production against Blastocystis hominis, an emerging infectious protozoan parasite which causes intestinal disorder in humans and animals, was studied. Sera and intestinal secretions were collected from B. hominis-immunized Balb/C mice for 8 weeks. Flow cytometry was used to monitor the levels of immunoglobulins A (IgA), G (IgG), and M (IgM) from both types of biological samples. The kinetic profile derived from flow cytometry analysis revealed that IgM led the early immune action against B. hominis infection in immune sera while IgA was the predominant antibody isotype in intestinal secretions. Western blotting revealed an array of antigens recognized by both serum and intestinal secretion antibodies. Immunoreactive B. hominis soluble proteins with molecular weights ranging from 28.2 to 77.6 kDa were detected by serum antibodies and 15.1 to 117.5 kDa by secretory antibodies. These antigens may be cytoplasmic or membrane-bound as determined through indirect fluorescent antibody test. Moreover, two immunogens (39.8 and 77.6 kDa) were commonly recognized by serum antibodies, one (70.8 kDa) by secretory antibodies and two (55.0 and 56.2 kDa) by both serum and secretory antibodies, suggesting a possible target in the further understanding of B. hominis pathogenicity, discovery of virulence factors, and development of immunology-based diagnostic protocols and alternative modes of treatment.
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PMID:Kinetic analysis of antibody responses to Blastocystis hominis in sera and intestinal secretions of orally infected mice. 1959 43

The gluten-sensitive enteropathy celiac disease is tightly associated with the production of autoantibodies specific for the enzyme transglutaminase 2 (TG2). The mechanisms underlying the activation of autoreactive B cells, however, are not well defined. To gain more insight into this autoimmune response we have characterized the binding of TG2 by a panel of human mAbs generated by expression cloning of Ig genes from single plasma cells of the celiac disease lesion. The Abs were highly specific to TG2 and bound preferentially to the open, Ca(2+)-activated enzyme conformation. Epitope mapping revealed that they recognize few distinct conformational epitopes that cluster in the N-terminal half of the enzyme. Two of the epitopes were overlapping with the fibronectin binding site in TG2, and none of the epitopes was accessible when TG2 was in a cell surface-bound form. Based on our findings, we propose that the autoantibodies are generated against the soluble, catalytically active enzyme, whereas Abs reactive with cell surface-associated TG2 are absent from the response due to negative selection of B cells recognizing membrane-bound self-Ag. The findings give insight into the mechanisms controlling the formation of anti-TG2 autoantibodies in celiac disease.
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PMID:Transglutaminase 2-specific autoantibodies in celiac disease target clustered, N-terminal epitopes not displayed on the surface of cells. 2369 Apr 78

The epithelial cell adhesion molecule gene (EPCAM, previously known as TACSTD1 or TROP1) encodes a membrane-bound protein that is localized to the basolateral membrane of epithelial cells and is overexpressed in some tumors. Biallelic mutations in EPCAM cause congenital tufting enteropathy (CTE), which is a rare chronic diarrheal disorder presenting in infancy. Monoallelic deletions of the 3' end of EPCAM that silence the downstream gene, MSH2, cause a form of Lynch syndrome, which is a cancer predisposition syndrome associated with loss of DNA mismatch repair. Here, we report 13 novel EPCAM mutations from 17 CTE patients from two separate centers, review EPCAM mutations associated with CTE and Lynch syndrome, and structurally model pathogenic missense mutations. Statistical analyses indicate that the c.499dupC (previously reported as c.498insC) frameshift mutation was associated with more severe treatment regimens and greater mortality in CTE, whereas the c.556-14A>G and c.491+1G>A splice site mutations were not correlated with treatments or outcomes significantly different than random simulation. These findings suggest that genotype-phenotype correlations may be useful in contributing to management decisions of CTE patients. Depending on the type and nature of EPCAM mutation, one of two unrelated diseases may occur, CTE or Lynch syndrome.
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PMID:EPCAM mutation update: Variants associated with congenital tufting enteropathy and Lynch syndrome. 3046 Nov 24